The term “haplotype block” is commonly used in the developing field of haplotype-based inference methods. We argue that the term should be defined based on the structure of the Ancestral Recombination Graph (ARG), which contains complete information on the ancestry of a sample. We use simulated examples to demonstrate key features of the relation between haplotype blocks and ancestral structure, emphasising the stochasticity of the processes that generate them. Even the simplest cases of neutrality or of a “hard” selective sweep produce a rich structure, often missed by commonly used statistics. We highlight a number of novel methods for inferring haplotype structure, based on the full ARG, or on a sequence of trees, and illustrate how they can be used to define haplotype blocks using an empirical dataset. While the arrival of computationally efficient methods makes it possible to apply these concepts broadly, existing and new methods could include tools for the identification and explore haplotype blocks, as we define them. Understanding and applying the concept of the haplotype block will be essential to fully exploit long and linked-read sequencing technologies.

Synteny, the ordering of sequences within homologous chromosomes, must be maintained within the genomes of sexually reproducing species for the sharing of alleles and production of viable, reproducing offspring. However, when the genomes of closely related species are compared, a loss of synteny can be observed. Synteny loss may be occurring due to transposon-mediated recombination errors during meiosis, unequal homologous recombination, resulting in the formation of chromosomal rearrangements. To examine patterns of synteny amongst three closely related, interbreeding, and wild Eucalyptus species, we assembled their genomes using long-read DNA sequencing and de novo assembly. We identify syntenic and rearranged regions between these genomes and estimate that ~48% of our genomes remain syntenic while ~36% is rearranged. We observed that rearrangements highly fragment micro-synteny, however genome-wide, macro-synteny appears to be maintained. Our results suggest that synteny between our species is primarily lost through small-scale rearrangements, not through sequence loss, gain, or sequence divergence. Further examination of identified rearrangements suggests that rearrangements may be altering the phenotypes of Eucalyptus species. Our study also questions the use of single reference genomes in genomic studies, reliance on a single reference genome when seeking genetic variation leads to reference bias, especially given the scale at which we show potentially adaptive loci have highly diverged, deleted, duplicated and/or rearranged. This study provides an unbiased framework to look at potential speciation and adaptive loci among a rapidly radiating foundation species of woodland trees that are free from selective breeding seen in most crop species.

Background. One- or two-day intervals are generally inserted into scheduled conditioning regimens for allogeneic hematopoietic cell transplantation (HCT), primarily due to various social circumstances, such as unexpected natural adversities, abrupt deterioration of patient health, and delays in graft source arrival. We compared the clinical outcomes of patients with interrupted conditioning to those with ordinarily scheduled conditioning. Procedure. We retrospectively analyzed 83 patients (children and adolescents) with oncologic disease who underwent myeloablative conditioning with total body irradiation (TBI). Interruption of conditioning was defined as a regimen in which one or two vacant days (no chemotherapy drug administration or TBI) were added to the initially scheduled regimen. Results. Overall and event-free survival were similar between the scheduled conditioning group and the interrupted conditioning groups (P = 0.955, P = 0.908, respectively). Non-relapse mortality and relapse rates were similar between the groups (P = 0.923, P = 0.946, respectively). The engraftment rate was not affected by interruption (P = 1.000). In contrast, the incidence of grade II–IV acute graft-versus-host disease (GVHD) reached a marginally significant difference between the groups (31% vs. 11%; P = 0.083). Conditioning interruption was identified to be an independent risk factor for chronic GVHD by multivariate analysis (odds ratio: 3.72; 95% CI: 1.04–13.3; P = 0.043). Conclusion. Apart from the incidence of chronic GVHD, clinical outcomes were not affected by one- or two-day intervals during conditioning.

Background. Low bone mineral density (osteopenia) is encountered in children with acute lymphoblastic leukemia (ALL) before, during and after treatment. Prior experience with alendronate, an oral bisphosphonate, demonstrated high tolerability and evident clinical efficacy. However, concerns have been expressed about the long-term safety and utility of such agents in children. Procedure. Of 217 children with ALL treated on Dana Farber Cancer Institute protocols 69 received alendronate for a mean of 87 weeks after dual energy X ray absorptiometry (DXA). DXA was repeated following completion of alendronate, and again 5-9 years later in a subgroup of 32 children. Lumbar spine areal bone mineral (LS aBMD) Z scores were obtained and values corrected for height, age and weight (HAW) were calculated for subjects 3-18 years of age. Results. Almost 80% (N=172) of the children remain in continuous complete remission at a mean of 14.5 years from diagnosis. Of those who receive alendronate, which was almost uniformly well tolerated, 7/69 (10.3%) relapsed compared to 19/89 (21.3%) who did not receive the drug. The mean unmodified LS aBMD Z score rose from -1.78 to -0.47. This gain was statistically significant for both unmodified (p <0.0001) and HAW corrected Z scores -1.32 to -0.42; p <0.0001). There was a modest median loss of LS aBMD (Z score 0.045) subsequently in the subgroup (N=32) of subjects on long-term follow up. Discussion. Alendronate appears to be well tolerated and moderately effective in osteopenic children with ALL. Whether it offers protection against relapse of leukemia needs further study.

With great sadness, we report that Haig Kazazian, Founding Co-Editor of Human Mutation, died on January 19, 2022 of complications related to congestive heart failure.

Electric circuit analysis under non-sinusoidal, non-linear situations has been a hot topic for a long time. Many scientific communities hold opposing viewpoints on the additional analysis tool and domain, resulting in a variety of standards and definitions. With the advent of Power Electronic equipment, converters, and Renewable Energy sources, the electric power system has become increasingly sophisticated since its inception. Electronic equipment has transformed the electrical system and provided a slew of advantages to industrial applications. Unfortunately, this comes at the expense of power system distortion (voltage and current). Understanding power flow in non-sinusoidal linear and non-linear circuit circumstances is required for this. As a result, a novel mathematical framework to analyze the circuit in such an environment is always required. Finally, in non-sinusoidal conditions, a consensus can be reached on norms that comply with well-known, established standards. The work provided here compares the use of harmonic domain and geometric algebra in circuits with disturbances for sinusoidal and non-sinusoidal excitations in order to demonstrate the accuracy of geometrical algebra in power flow calculations.

The phylogeography of the American black bear (Ursus americanus) is characterized by isolation into glacial refugia, followed by population expansion and genetic admixture. Anthropogenic activities, including overharvest, habitat loss, and transportation infrastructure, have also influenced their landscape genetic structure. We describe the phylogeography of the American black bear in the American Southwest and northern Mexico and investigate how prehistoric and contemporary forces shaped genetic structure and influenced gene flow. Using a suite of microsatellites and a sample of 550 bears, we identified 14 subpopulations organized hierarchically following the distribution of ecoregions and mountain ranges containing black bear habitat. The pattern of subdivision we observed is more likely a product of postglacial habitat fragmentation during the Pleistocene and Holocene, rather than a consequence of contemporary anthropogenic barriers to movement during the Anthropocene. We used linear mixed-effects models to predict genetic distance among individuals, which indicated that both isolation by resistance and geographic distance govern gene flow. Gene flow was highest among subpopulations occupying large tracts of contiguous habitat, was reduced among subpopulations in the Madrean Sky Island Archipelago, where montane habitat exists within a lowland matrix of arid lands, and was essentially nonexistent between two isolated subpopulations. We found significant asymmetric gene flow supporting the hypothesis that bears expanded northward from a Pleistocene refugium located in the American Southwest and northern Mexico and that major highways were not yet affecting gene flow. The potential vulnerability of the species to climate change, transportation infrastructure, and the U.S.-Mexico border wall highlights conservation challenges and opportunities for binational collaboration.

Porocarcinoma is a rare type of skin cancer that develops from the intraepidermal ductal part of eccrine sweat glands. It can arise de novo or from poroma ground with high potential for locoregional metastatic spread, morbidity, and mortality. It mostly occurs in elderly patients.

We report the case of a patient for whom surgical hemostasis of gastrointestinal bleeding from a splenic artery pseudoaneurysm that developed due to gastric ulcer penetration was achieved with resuscitative endovascular balloon occlusion of the aorta.

Acinetobacter baumannii is an aerobic gram-negative bacillus and nosocomial pathogen that predominantly affects individuals in the ICU. We present a case of a patient without any known medical problems or recent hospitalizations presenting with Acinetobacter baumannii bacteremia and a concomitant spontaneous fungal peritonitis in the setting of newly diagnosed cirrhosis

If an initial frame of vectors $\{e_i\}$ is related to a final frame of vectors $\{f_i\}$ by, in geometric algebra (GA) terms, a {\it rotor}, or in linear algebra terms, an {\it orthogonal transformation}, we often want to find this rotor given the initial and final sets of vectors. One very common example is finding a rotor or $4\times 4$ orthogonal matrix representing rotation and translation, given knowledge of initial and transformed points. In this paper we discuss methods in the literature for recovering such rotors and then outline a GA method which generalises to cases of any signature and any dimension, and which is not restricted to orthonormal sets of vectors. The proof of this technique is both concise and elegant and uses the concept of {\it characteristic multivectors} as discussed in the book by Hestenes \& Sobczyk, which contains a treatment of linear algebra using geometric algebra. Expressing orthogonal transformations as rotors, enables us to create {\it fractional transformations} and we discuss this for some classic transforms. In real applications, our initial and/or final sets of vectors will be noisy. We show how to use the characteristic multivector method to find a ‘best fit’ rotor between these sets and compare our results with other methods.

An epiploic appendix torsion is a rare event that can lead to acute abdominal pain and occurs at any age. Chiropractic is a type of complementary medicine performed explicitly by spinal manipulations. In this report, we presented a case who developed acute abdominal pain after spinal manipulation.

Background and Purpose: Traumatic hemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of TCA inhibitor (nomacopan) on organ damage and survival in vivo. Experimental Approach: Complement activation products and cytokines were analyzed in plasma from 54 combat casualties, and the correlations between activated complement pathway(s) and the clinical outcomes in trauma patients were assessed. Nomacopan was administrated to rats subjected to lethal TH (blast injury and hemorrhagic shock). Effects of nomacopan on TH were determined using survival rate, organ damage, physiologic parameters, and laboratory profiles. Key Results: Early TCA was found to be associated with systemic inflammatory responses and clinical outcomes in this trauma cohort. Lethal TH in the untreated rats induced early TCA that correlated with severity of tissue damage and mortality. The addition of nomacopan to a damage control resuscitation (DCR) protocol significantly inhibited TCA, decreased local and systemic inflammatory responses, improved hemodynamics and metabolism, attenuated tissue and organ damage, and increased survival. Conclusion and Implications: Our findings reveal that early TCA represents a rational therapeutic target for trauma patients; and nomacopan as a prosurvival and organ-protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities.

As establishing a foundation for a new line of investigations on threshold secret sharing schemes with geometric algebra (GA), we propose a variation of a well-known threshold secret sharing scheme introduced by Adi Shamir in 1979, a cryptographic solution that allows a secret input to be divided into multiple random shares which are then sent, each one, to distinct parties. The computation of these shares is done so that there are proper subsets of these shares that allow reconstructing the secret input using polynomial interpolation. To reconstruct the secret input, Shamir’s scheme requires a minimum number of shares, smaller than the total number of shares, referred to as a threshold. Any number of shares smaller than the threshold reveals nothing about the input secret. The random shares are generated such that each party can perform computations, generating a new set of shares that, when reconstructed, are equivalent to performing those exact computations directly on the secret input data. Our variant replaces the algebra in which the original secrets lie from integers to GA while preserving fundamental properties in Shamir’s scheme, such as perfect secrecy and idealness (both secret and random shares are members of the same space). As a direct result, any application in GA dealing with multivectors can immediately add threshold security using our scheme. Non-GA applications can also benefit from our results by using multivectors as a vessel for sharing multiple secrets at once.

Different ways of representing the group $SU(3)$ within a Geometric Algebra approach are explored. As part of this we consider characteristic multivectors for $SU(3)$, and how these are linked with decomposition of generators into commuting bivectors. The setting for this work is within a 6d Euclidean Clifford Algebra. We then go on to consider whether the fundamental forces of particle physics might arise from symmetry considerations in just the 4d geometric algebra of spacetime --- the STA. As part of this, a representation of $SU(3)$ is found wholly within the STA, involving preservation of a bivector norm. We also show how Octonions can be fully represented within the Spacetime Algebra, which we believe will be useful in making them understandable and accessible to a new community in Physics and Engineering. The two strands of the paper are drawn together in showing how preserving the octonion norm is the same as preserving the timelike part of the Dirac current of a particle. This suggests a new model for the symmetries preserved in particle physics. Following on from work by G\"unaydin and G\"ursey on the link between quarks, and octonions, and by Furey on chains of octonionic multiplications, we show how both of these fit well within our scheme, and give some wholly STA versions of the operations involved, which in the cases considered have easily understandable equivalents in terms of 4d geometry. Links with larger groups containing $SU(3)$, such as $G_2$ and $SU(8)$, are also considered.

Suspicions about medical murder sometimes arise due to a surprising or unexpected series of events, such as an apparently unusual number of deaths among patients under the care of a particular nurse. But also a single disturbing event might trigger suspicion about a particular nurse, and this might then lead to investigation of events which happened when she was thought to be present. In either case, there is a statistical challenge of distinguishing event clusters that arise from criminal acts from those that arise coincidentally from other causes. We show that an apparently striking association between a nurse's presence and a high rate of deaths in a hospital ward can easily be completely spurious. In short: in a medium-care hospital ward where many patients are suffering terminal illnesses, and deaths are frequent, most deaths occur in the morning. Most nurses are on duty in the morning, too. There are less deaths in the afternoon, and even less at night; correspondingly, less nurses are on duty in the afternoon, even less during the night. Consequently, a 1 full time nurse works the most hours when the most deaths occur. The death rate is higher when she is present than when she is absent.

In the last decade, real time PCR has been increasingly adopted for bluetongue diagnosis with both broadly reactive and serotype-specific assays widely used. The use of these assays and nucleic acid sequencing technologies have enhanced bluetongue virus detection, resulting in the identification of a number of new serotypes. As a result, more than 30 different serotypes are proposed. Rapid identification of the virus serotype is essential for matching of antigens used in vaccines and to undertake surveillance and epidemiological studies to assist risk management. However, it is not uncommon for multiple serotypes to circulate in a region either concurrently or in successive years. It is therefore necessary to have a large suite of assays available to ensure that the full spectrum of viruses is detected. Nevertheless, covering a large range of virus serotypes is demanding from both a time and resource perspective. To overcome these challenges, real time PCR assays were optimised to match local virus strains and then combined in a panel of quadriplex assays, resulting in 3 assays to detect 12 serotypes directly from blood samples from cattle and sheep. These multiplex assays have been used extensively for bluetongue surveillance in both sentinel animals and opportunistically collected samples. A protocol to adapt these assays to capture variations in local strains of bluetongue virus and to expand the panel is described. Collectively these assays provide powerful tools for surveillance and the rapid identification of bluetongue virus serotypes directly from animal blood samples.

There are different dynamic characteristics in each stage of rail transit network development. It can provide guidance for rail transit network planning and phased construction,Evaluating the evolution degree of urban rail transit network and accurately dividing the evolution stages. Starting from the allometric growth relationship between transfer nodes and ordinary nodes in urban rail transit network, this paper defines the evolution level of rail transit network and the growth rate difference between transfer and ordinary nodes, and deduces the logistic dynamic equation of urban rail transit network evolution level with the help of mathematical derivative and logarithmic relationship, This paper reveals the dynamic law of the evolution process of urban rail transit network from the theoretical level, analyzes the evolution dynamic process on this basis, finds the Threshold for phasing the evolution stage, and divides it into four evolution stages. Finally, the theoretical derivation results are verified with the evolution data of Beijing Rail Transit Network (1984-2020) for 45 years. The verification results are highly consistent with the theoretical derivation results, which proves the correctness of the theoretical model and its practical guiding significance for the construction of rail transit network.

In this paper we present a new discrete retarded Gronwall-Bellman type inequality. As applications, the dynamics of some delay difference equations are studied. First, the asymptotic behavior of solutions for scalar difference equation $\Delta x(n)=-a(n)x(n)+B(n,x_n)$ is discussed, and some new criterion on the asymptotic stability of the zero solution are obtained under weaker assumptions. Then the dissipativity of a nonautonomous delay difference system with superlinear nonlinearities is investigated. By using the inequalities established here, it is shown that the discrete set-valued process generated by the system possesses a unique global pullback attractor.

Here, from macrophylogeographic mtDNA empirical data, we proposed a scenario of the evolution and speciation of two important forest trees, European Black Pine and Scotch Pine, and their multiple subspecies and varieties. Molecular clock simulations revealed that INDELs variability in the Pinus mitochondrial genome is relatively old, i.e., from the Pliocene-Miocene epoch, and related to historical tectonic continental fluctuations rather than climate change on a large geographic scale. Special attention is paid to the relationships between different speciation models and historical migration patterns and between peripheral and central populations. Species evolution involves the mixing of different speciation modes rather than only one of them, and one speciation mode has different results/effects on different DNA types (e.g., mitochondrial vs. chloroplast vs. nuclear DNA). The misbalance between different meta-population census size vs. effective population size contributions for asymmetric migration pattern is a result of different genotypes (and sub-phylogenetic lines) responding to selection pressing and adaptive evolution.

In this work, we study the very weak solution for the stationary exterior Stokes problem with Navier slip boundary condition. We try to investigate some results of the existence and the uniqueness of solutions related to this problem in an exterior domain in $L^p-$theory where $1

Porcine Deltacoronavirus (PDCoV) is an emergent swine coronavirus that infects epithelia cells from the small intestine, and inducing watery diarrhea, vomiting and dehydration. Clinical signs are more aggressive in piglets causing high mortality rates (>40%) representing serious economic losses. Despite the importance of PDCoV as an emerging coronavirus, little is known about the currently prevalence in México. We select from GenBank a group of 138 sequences and obtained a consensus PDCoV membrane protein (M-PDCoV) sequence of 216 a.a. A Maximum Likelihood phylogenetic tree was constructed and evaluate the relationship between the 138 sequences. Also, a protein tertiary structure analysis was performed to analyze and compare the topological differences. The phylogeny and the tertiary structure analysis showed that M-PDCoV is highly conserved and therefore suitable to use as an antigen in a diagnostic system. Hence, an expression system performed in E. coli BL21 (DE3) using the vector pET-SUMO with a His-tag was prepared, resulting in a synthetic M gene of 654 pb to produce a recombinant M-PDCoV protein ( rM-PDCoV). Western blot test confirmed the rM-PDCoV immune detection in 8 of 17 sera samples. The rM-PDCoV was able to successfully stimulate immune response in immunized mice to produce antibodies after day 7 of immunization (P < 0.001). Our results show that rM-PDCoV is suitable to use in diagnostic systems like an ELISA.

Harlequin syndrome corresponds to unilateral dysfunction of sympathetic system, characterized by flush and unilateral hyperhidrosis associated with hypo or anhidrosis and paleness of the opposite side. It is, usually, idiopathic. Rarely, it may be associated with compressive organic processes, iatrogenic causes and general diseases. It is a real therapeutic challenge.

Phantosmia is the sensation of a fragrance intermittently or continuously when no odorant trigger is available. Without any further complaints, COVID-19 individuals may experience olfactory hallucination. Phantosmia was unnoticed for a long time sinc